Effective and efficient delivery of drugs is an important area of research in pharmaceutical industry due to the significant challenges related to the physiological properties of therapeutics. For example, biomolecular therapeutics degrade by proteolytic enzymes and hence can only remain in the plasma circulation for a short period of time therefore higher dose use is required. In order to overcome those and such problems functional and responsive polymeric network structures as delivery vehicles for controlled drug release are being developed. And sequential delivery of drugs with altered hydrophobicities is achieved via responsiveness to specific stimuli. Polymeric hydrogels are attracting special attention due to their biocompatible character, capacity to retain water, and permeable structures. As a result they have been increasingly used in biomedical and pharmaceutical applications including drug delivery systems. Stimuli responsive hydrogel networks also referred as smart materials can exhibit desirable physicochemical properties depending on their collapsed or swollen states. These properties change significantly in response to changes in environmental properties such as elevated temperatures, wavelength of light, electric field, ionic strength and pH. Particularly, pH sensitive hydrogels can detect changes in environmental pH that causes corresponding, modification on the physical properties of hydrogels such as shape and size. pH sensitive hydrogels are specifically useful for oral administration of the drug along the digestive tract due to the drastically different pH conditions observed at different locations, or for targeted drug delivery into tumor site due to alterations in the acidity of the tumor tissues.
Poly(methacrylic acid-grafted-Ethylene Glycol) (P(MAA-g-EG)) hydrogels are known to be used as pH responsive polymeric networks. And also in prior art, there are studies regarding to functionalization of P(MAA-g-EG) hydrogels, especially for sequential delivery of therapeutics. A combination of a stimuli responsive hydrophilic network with a less hydrophilic component might have the potential to provide site specific and sustained drug delivery. For example, in a study by Schomer et al. that was published in 2012, light mediated polymerization is used for the synthesis of both P(MAA-g-EG) hydrogels dispersed with poly methylmethacrylate) (PMMA) nanoparticles and amphiphilic interpenetrating networks (IPNs) of P(MAA-g-EG) and poly(n-butyl acrylate) PBA and their use as the oral drug delivery agents for pharmaceutical use was enclosed in the study as well. (Schomer C A, Hutson H N, Peppas N A. J Biomed Mater Res Part A 2012; 101:2229-36.) Photoinitiated free radical polymerization using UV light is a widely used method for the synthesis of P(MAA-g-EG) hydrogels. Although this method works efficiently, high amounts of photo initiators and co-initiators are being used which affects the biocompatible character of the resulting hydrogel.
It is apparent that there is a substantial need for a biocompatible, functionalized, effective, responsive hybrid hydrogels to be used in drug delivery applications and an efficient way of synthesizing such hydrogels. Here, in this invention visible light induced photopolymerization of pH responsive composite P(MAA-g-EG) hydrogel is suggested as a drug delivery vehicle for controlled release applications and by this method lesser amount of initiator is used and shorter reaction time is realized. The resulting polymer is functional, has improved integity, enhanced biocompatibility and advanced swelling properties.